SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance.

Abstract

Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions. Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance. Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure. Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle. Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone leptin. Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity. Our results unveil important protective roles of SIRT1 in SF1 neurons against dietary metabolic imbalance.

• Authors: Giorgio Ramadori, Teppei Fujikawa, Jason Anderson, Eric D Berglund, Renata Frazao, Shaday Michán, Claudia R Vianna, David A Sinclair, Carol F Elias, Roberto Coppari
• Journal: Cell metabolism (Cell Metab) Vol. 14 Issue 3 Pg. 301-12 (Sep 07 2011) ISSN: 1932-7420 [Electronic] United States
• PMID: 21907137 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Dietary Fats
• Insulin
• Intracellular Signaling Peptides and Proteins
• Leptin
• Neuropeptides
• Orexins
• Steroidogenic Factor 1
• Sirt1 protein, mouse
• Sirtuin 1

Topics

• Animals
• Diabetes Mellitus, Type 2 (complications, metabolism, pathology)
• Diet, High-Fat (adverse effects)
• Dietary Fats (metabolism, pharmacology)
• Energy Metabolism
• Female
• Gene Expression
• Gene Knockdown Techniques
• Hypothalamus (cytology, drug effects, metabolism)
• Immunohistochemistry
• Insulin (metabolism, pharmacology)
• Insulin Resistance
• Intracellular Signaling Peptides and Proteins (pharmacology)
• Leptin (pharmacology)
• Mice
• Mice, Transgenic
• Motor Activity (drug effects)
• Neurons (cytology, drug effects, metabolism)
• Neuropeptides (pharmacology)
• Obesity (complications, metabolism, pathology)
• Orexins
• Patch-Clamp Techniques
• Sirtuin 1 (deficiency, genetics)
• Steroidogenic Factor 1 (genetics, metabolism)